The CD95/CD95L signaling pathway: A role in carcinogenesis

• Published in: Biochimica et biophysica acta Vol. 1846; no. 1; pp. 130 - 141
• Main Authors: Fouqué, Amélie, Debure, Laure, Legembre, Patrick
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2014; Elsevier
• Subjects: Animals; Apoptosis; Carcinogenesis; Carcinogenesis - genetics; Cytokine; Fas; Fas Ligand Protein - physiology; fas Receptor - physiology; Humans; Inflammation; Life Sciences; Receptors, Tumor Necrosis Factor - physiology; Signal Transduction - physiology; Fas; Inflammation; Carcinogenesis; Cytokine; Apoptosis
• ISSN: 0304-419X; 0006-3002; 1879-2561; 1878-2434
• DOI: 10.1016/j.bbcan.2014.04.007

Apoptosis is a fundamental process that contributes to tissue homeostasis, immune responses, and development. The receptor CD95, also called Fas, is a member of the tumor necrosis factor receptor (TNF-R) superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance, and various lineages of malignant cells exhibit loss-of-function mutations in this pathway; therefore, CD95 was initially classified as a tumor suppressor gene. However, more recent data indicate that in different pathophysiological contexts, this receptor can transmit non-apoptotic signals, promote inflammation, and contribute to carcinogenesis. A comparison with the initial molecular events of the TNF-R signaling pathway leading to non-apoptotic, apoptotic, and necrotic pathways reveals that CD95 is probably using different molecular mechanisms to transmit its non-apoptotic signals (NF-κB, MAPK, and PI3K). As discussed in this review, the molecular process by which the receptor switches from an apoptotic function to an inflammatory role is unknown. More importantly, the biological functions of these signals remain elusive. [Display omitted] •The CD95/CD95L pair contributes to inflammation and carcinogenesis.•At least two CD95 ligands exist with two different pathophysiological roles.•CD95 recruits receptor tyrosine kinases to induce non-apoptotic signaling pathways.•In vivo roles of CD95 should be reinterpreted including its non-apoptotic function.